Profile and kinetics of L-type calcium current during the cardiac ventricular action potential compared in guinea-pigs, rats and rabbits

Abstract.

The substantial interspecies differences in mammalian cardiac action potentials (APs) are attributed primarily to variations in K⁺ currents. In a comparative study on isolated ventricular myocytes from guinea-pigs, rabbits and rats, we investigated the influence of the species-based AP differences on the time course of the L-type Ca²⁺ current (I _Ca,L). In addition, we tested whether also species-dependent properties of the I _Ca,L contribute to its time course during the AP. In patch-clamp measurements, I _Ca,L was characterised using conventional square pulses and digitised APs as command voltages. Special interest was directed to the analysis of the actual time courses of I _Ca,L, and L-type channel activation and inactivation during APs. Although species-specific differences in AP shape strongly influence the amplitude and the time course of I _Ca,L, divergence in L-type channel inactivation was found as well. In each species I _Ca,L inactivation was related to Ca²⁺ influx via L-type channels. However, while L-type channels showed similar Ca²⁺ dependency in the rabbit and the rat, a 2-times higher Ca²⁺ influx was necessary to achieve a given degree of inactivation in the guinea-pig. Thus, inactivation of I _Ca,L is delayed in the guinea-pig, thereby contributing to the prolonged AP plateau in this species. Comparing the actual time course of I _Ca,L, and L-type channel activation and inactivation revealed that, in each species, fading of I _Ca,L during final repolarisation was caused by deactivation (i.e. closure of the channel's d-gate) rather than inactivation.